TET1 involved in bisphenol A induced TM3 Leydig cell toxicity by regulating Cav3.3 hydroxymethylation

• Published in: Chemosphere (Oxford) 2023-01, Vol.312, p.137171, Article 137171
• Main Authors: Zhou, Shi-meng, Yuan, Wen-bo, Li, Jing-zhi, Chen, Hong-qiang, Zeng, Yong, Wang, Na, Fan, Jun, Zhang, Zhe, Xu, Yuanyuan, Cao, Jia, Liu, Wen-bin
• Format: Article
• Language: English
• Subjects: Bisphenol A; Cav3.3; Reproductive toxicity; TET1 gene; TM3 Leydig cells
• ISSN: 0045-6535; 1879-1298
• DOI: 10.1016/j.chemosphere.2022.137171

Bisphenol A (BPA), an important environmental pollutant, is known to damage reproductive development. However, the underlying epigenetic mechanism in Leydig cells during BPA exposure has not been explored in detail. In this study, TM3 Leydig cells were treated with BPA (0, 20, 40 and 80 μM) for 72 h. The differentially expressed TET1 cell model was constructed to explore the mechanism of BPA-induced cytotoxicity. Results showed that BPA exposure significantly inhibited cell viability and increased apoptosis of TM3 Leydig cells. Meanwhile, the mRNA of TET1, Cav3.2 and Cav3.3 decreased significantly with the increase of BPA exposure. Importantly, TET1 significantly promoted proliferation of TM3 Leydig cells and inhibited apoptosis. Differentially expressed TET1 significantly affected BPA-induced toxicity in TM3 Leydig cells. Notably, TET1 elevated the mRNA levels of Cav3.2 and Cav3.3. MeDIP and hMeDIP confirmed that TET1 regulated the expression of Cav3.3 through DNA hydroxymethylation. Our study firstly presented that TET1 participated in BPA-induced toxicity in TM3 Leydig cells through regulating Cav3.3 hydroxymethylation modification. These findings suggest that TET1 acts as a potential epigenetic marker for reproductive toxicity induced by BPA exposure and may provide a new direction for the research on male reproductive damage. [Display omitted] •BPA exposure leads to down-regulation of TET1 gene expression in TM3 cells.•Knockdown of TET1 aggravates the cytotoxicity of BPA to TM3 cells.•Knockdown of TET1 inhibits the expression of Cav3.2 and Cav3.3.•TET1 regulates Cav3.3 expression through hydroxymethylation in TM3 cells.